Kinds of Grafts
definitions
Core Vocabulary
- Graft — cells, tissue, or an organ moved from a donor into a recipient
- Transfusion — the graft is circulating blood cells or plasma, the most common transplant procedure in practice
Classified by Genetic Relationship
| Graft type | Relationship | Example |
|---|---|---|
| Autograft | Same individual, different site | Skin graft for burns; saphenous vein used in bypass |
| Isograft (syngeneic) | Genetically identical individuals | Between monozygotic twins |
| Allograft | Same species, genetically distinct | Kidney transplant |
| Xenograft | Different species | Porcine heart valve into a human |
One Rule Worth Memorizing
- Autografts are the only category never rejected, since donor and recipient tissue are the same individual.
- Every other category carries rejection risk and generally needs some degree of lifelong immune suppression.
Even Isografts Aren't Always Silent
- Identical twins can still show subtle antigenic mismatch
- Cause: somatic mutations acquired after the twins diverge developmentally
Why Foreign Tissue Gets Noticed
mechanism
The Molecular Basis
- Recognition of self vs. foreign tissue hinges on the major histocompatibility complex (MHC)
- MHC genes are extremely polymorphic across the population
- MHC genes are inherited codominantly
- One full haplotype comes from each parent
- Two unrelated people will almost always differ at these loci
Consequence
- Any non-autograft is eventually flagged as foreign
- Recipient immune cells destroy it through graft rejection unless suppressed
How the Attack Unfolds
Graft vascularizes→
Host CD4+/CD8+ cells infiltrate→
Sensitization to major + minor MHC differences→
Effector-phase killing
Effector Phase Details
- Helper T cytokines recruit macrophages, cytotoxic T cells, and antibody-mediated killing
- Interferons and TNF raise class I MHC expression on graft cells
- Interferon-gamma additionally raises class II MHC expression
- Net effect: graft cells become progressively easier targets for MHC-restricted killing
- All rejection syndromes are distinguished mainly by two variables: how fast they start and which effector arm dominates.
Minutes-to-Hours Rejection
Hyperacute
Timing & Trigger
- Onset: minutes to hours after graft perfusion
- Caused by antibody that already exists before transplant
- Prior sensitizing events
- Earlier transfusions
- Multiple pregnancies
- A previous transplant
- Corresponds to a type II (cytotoxic) hypersensitivity reaction
What the Antibody Does
Preformed antibody binds graft endothelium→
Complement activation→
Clotting cascade triggered→
Thrombosis + ischemic necrosis
- Rare in real practice because donor-recipient cross-matching screens for this antibody beforehand.
- Despite being rare clinically, it is a frequent exam vignette — treat "rejection within minutes" as the signature clue.
Days-to-Weeks Rejection
Acute & Accelerated
Standard Acute Rejection
- Onset: days to weeks
- Behaves like a primary adaptive immune response — this is the first time the host meets this graft's antigens
- Driven mainly by alloantigens, predominantly MHC molecules on the graft
- Both CD4+ and CD8+ T cells participate; antibody contributes too
- The main rejection type that immunosuppressive drugs are designed to prevent
Accelerated Acute Rejection
- Onset: compressed to just days
- Behaves like a memory (secondary) response rather than a first encounter
- Implies prior sensitization to this graft's antigens, just not enough preformed antibody to cause hyperacute rejection
Tissue-Level Picture
- Parenchymal cell injury with interstitial inflammation
- Endothelialitis — lymphocytes infiltrating and damaging the vessel lining
Slow, Late Rejection
Chronic
Timing & Course
- Onset: months to years after transplant
- Predominantly T-cell mediated
- Notoriously hard to reverse once established
- Usually ends in eventual graft loss
- Underlying trigger poorly defined — viral infection is one suspected contributor
What Happens Inside the Vessel Wall
Alloantigen-specific CD4+ T cells persist→
Chronic low-grade delayed-type reaction→
Smooth-muscle proliferation in the vessel wall→
Progressive vessel occlusion
- Unlike hyperacute or acute rejection, chronic rejection is a vascular remodeling problem more than an acute cytotoxic event.
| Rejection type | Onset | Dominant mechanism |
|---|---|---|
| Hyperacute | Minutes–hours | Preformed antibody + complement |
| Acute | Days–weeks | Primary T-cell / antibody response |
| Accelerated acute | Days | Memory T-cell / antibody response |
| Chronic | Months–years | T-cell-driven vascular remodeling |
When the Graft Attacks Back
GVHD
Why Bone Marrow Is a Special Case
- Bone marrow supplies pluripotent hematopoietic stem cells
- Used to rebuild myeloid, erythroid, and lymphoid lineages after they've been wiped out by malignancy or chemotherapy
- Problem: the marrow inoculum also carries mature donor T lymphocytes
The Reversal of the Usual Direction
Donor T cells enter host→
Recognize host MHC as foreign→
Attack host epithelium
Clinical Picture
- Widespread epithelial cell death
- Skin — rash
- Liver — jaundice
- Gut — diarrhea and GI hemorrhage
- Preventive step: donor marrow is depleted of mature T cells before infusion to reduce graft-versus-host risk.
Holding Immunity in Check
Pharmacology
Classic Small-Molecule Backbone
- Corticosteroids
- Cyclosporine A
- Rapamycin (sirolimus)
Where Monoclonals Fit In
- Used alongside the classic agents for both prevention and treatment of rejection
- Each targets a distinct step in T-cell activation or survival
| Agent | Molecular target | Mechanism |
|---|---|---|
| Daclizumab, basiliximab | IL-2 receptor | Blocks IL-2 binding; opsonizes IL-2R+ cells, halting T-cell proliferation |
| Muromonab | CD3 | Blocks T-cell activation and drives T cells into apoptosis |
| Belatacept | CTLA-4-Ig fusion protein | Binds B7, preventing it from engaging CD28 costimulation |
| Alemtuzumab | CD52 (pan-lymphocyte marker) | Binds lymphocytes and triggers complement-mediated lysis, depleting the T-cell pool |
- Belatacept's target, the B7–CD28 costimulatory link, is the same checkpoint that regulatory T cells exploit via CTLA-4 to dampen ordinary autoimmune responses.